Industrial preparation method and application of high-purity alpha-aminonitrile

Abstract

The application relates to an industrialized preparation method and application of high-purity alpha-amino nitrile. The application belongs to the technical field of fine chemical synthesis. The purpose of the application is to solve the technical problems of low yield and purity, high cost and unsuitability for industrialized production of the existing alpha-amino nitrile synthesis method. The method of the application is as follows: taking imine as a substrate, alpha-amino nitrile is synthesized by reacting with acetone cyanohydrin under the action of an ionic liquid. The method of the application synthesizes a nucleophilic addition cyanyl product of a carbon-nitrogen double bond in one step at room temperature. By selecting the ionic liquid and reasonably controlling the proportioning of various substances, the reaction process is greatly accelerated, the high-efficiency synthesis of alpha-amino nitrile is realized, the purity of alpha-amino nitrile is remarkably improved, the substrate adaptability is good, and the method can be widely applied to the synthesis in the fields of medicines and the like in the industry and the academia.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical synthesis technology, specifically relating to an industrial preparation method and application of high-purity α-aminonitrile. Background Technology

[0002] α-Aminonitriles are important intermediates in organic synthesis, with wide applications in chemistry and biology. They can be used to synthesize various amino acids, amides, diamines, and nitrogen-containing heterocyclic compounds. Due to their excellent chemical and biological properties and the potential for chiral structures, α-aminonitriles can be used to synthesize antithrombotic drugs, anticancer drugs, etc. Therefore, studying the synthetic methods of these compounds is not only of great significance to organic synthesis methodology, but also has high potential value and research significance in fields such as medicine, biology, and materials science. The addition of cyanide reagents to unsaturated carbon-nitrogen double bonds is the main route for preparing α-aminonitriles, and the selection of cyanide reagents is constantly being optimized as research into this reaction deepens. Acetone cyanohydrin, as a byproduct of acrylonitrile production, has attracted researchers' attention due to its low price, miscibility with water and many organic solvents, and the fact that the only byproduct after the reaction is acetone, making it suitable for industrial production. Compared to acetone cyanohydrin, hydrogen cyanide is more toxic and difficult to transport, posing a greater threat to the environment and the health of researchers. While the toxicity of metal hydrides has decreased significantly, they still suffer from poor solubility in organic solvents. Organic cyaniding reagents such as trimethylcyanosilane (TMSCN) have problems such as low atom utilization, high price, and suitability only for small-scale laboratory tests, making them unsuitable for industrial production.

[0003] Currently, the most direct route for preparing α-aminonitrile is the addition reaction of the cyano group with the carbon-nitrogen double bond, such as the one-pot reaction using trimethylcyanosilane as the cyanide source and aldehydes and amines as raw materials. However, this method has the following problems: 1. Most methods are one-pot, resulting in impure target products, residual aldehydes that easily generate other byproducts, complex operation, harsh conditions, and high purification difficulty; 2. TMSCN is often used as the cyaniding reagent, widely favored for its high activity and low toxicity, but its high price and low atom economy make it suitable only for small-scale laboratory tests and not for industrial production; 3. It requires the addition of organic solvents, most of which are highly volatile, posing significant harm to the environment and operators; 4. The use of alkaline catalysts makes them impossible to recycle and reuse, harming the environment and operators; 5. The reaction system using ionic liquids has a long reaction time and poor substrate applicability, with a limited range of applicable amines, and aliphatic amines are not suitable. Therefore, it is necessary to develop a green, safe, efficient, and rapid method for preparing α-aminonitrile. Summary of the Invention

[0004] To overcome the shortcomings of the prior art, the present invention provides an industrial preparation method and application of high-purity α-aminonitrile.

[0005] The technical solution of the present invention is as follows:

[0006] One objective of this invention is to provide an industrial method for preparing high-purity α-aminonitrile, the method comprising the following steps:

[0007] α-aminonitrile was synthesized by reacting imine with acetone cyanohydrin under the action of ionic liquid.

[0008] Further specifying, the imine is N-benzylbenzylamine, N-benzyl-p-tolylmethylamine, N-benzyl-p-ethylphenylmethylamine, N-benzyl-p-chlorophenylmethylamine, N-benzyl-1-(furan-2-yl)methylamine, N-benzyl-1-(thiophen-2-yl)methylamine, N-benzyl-p-fluorophenylmethylamine, N-benzyl-p-isopropylphenylmethylamine, N-benzyl-1-(3-pyridyl)methylamine, N-benzyl-1-(2-pyridyl)methylamine, N-n-butyl-p-tolylmethylamine, N-benzyl-o-chlorophenylmethylamine, N-benzyl-m-chlorophenylmethylamine, N-benzyl-p-cyanophenylmethylamine, N-cyclohexyl-p-tolylmethylamine, N-cyclohexylmethyl-p-tolylmethylamine, or N-1-(2-furanmethyl)-p-tolylmethylamine.

[0009] Further specifying, the ionic liquid is 1-butyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium perchlorate, 1-ethyl-3-methylimidazolium acetate, or 1-butyl-3-methylimidazolium bromide.

[0010] Further specified, the amount of acetone cyanohydrin used is 1.0-2.0 times the equivalent of imine, and the amount of ionic liquid used is 0.5-2.0 times the equivalent of imine.

[0011] Furthermore, the amount of acetone cyanohydrin used is 1.5-2.0 times the equivalent of imine, and the amount of ionic liquid used is 1.0-2.0 times the equivalent of imine.

[0012] The optimal choice is to use acetone cyanohydrin at a rate of 1.5 times the equivalent of the ionic liquid.

[0013] Further, the reaction temperature is specified as 25-50℃.

[0014] A second objective of this invention is to provide an α-aminonitrile prepared by the above method, wherein the general structural formula of the α-aminonitrile is:

[0015]

[0016] In the formula, R1 represents phenyl, 4-Me-phenyl, 4-Et-phenyl, 4-Br-phenyl, 4-Cl-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-i-pr-phenyl, furanl, 4-methylbenzonitrile, 2-methylpyridine or 3-methylpyridine; R2 represents toluene, butane, cyclohexane, methylcyclohexane or 2-methylfuran.

[0017] Furthermore, the purity of the α-aminonitrile is >99%.

[0018] The third objective of this invention is to provide an application of the above-mentioned α-aminonitrile as an intermediate in the chemical, biological and pharmaceutical fields.

[0019] The advantages of this invention compared to the prior art are:

[0020] This invention starts with imines, using inexpensive acetone cyanohydrin as the cyanide source. Under the influence of a green and pollution-free ionic liquid, it achieves a one-step synthesis of nucleophilic addition cyanide products of carbon-nitrogen double bonds at room temperature, eliminating the need for cumbersome procedures. By selecting the ionic liquid and simultaneously controlling the rational proportions of each substance, the reaction process is greatly accelerated, achieving not only efficient synthesis of α-aminonitriles but also significantly improving their purity, with the obtained α-aminonitriles exhibiting a purity greater than 99%. Furthermore, no additional solvent is added, making it green, safe, and recyclable. The method of this invention has good substrate adaptability and can be widely applied in the synthesis of pharmaceuticals and other fields in industry and academia. Attached Figure Description

[0021] Figure 1 The infrared spectrum of 2-benzylamino-2-phenylacetonitrile obtained in Example 1;

[0022] Figure 2 The 2-benzylamino-2-phenylacetonitrile prepared in Example 1 1 HNMR spectrum. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0024] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the materials, reagents, methods, and instruments used are all conventional materials, reagents, methods, and instruments in the art, and can be obtained commercially by those skilled in the art.

[0025] The terms “comprising,” “including,” “having,” “containing,” or any other variations thereof, as used in the following embodiments, are intended to cover a non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that includes the listed elements is not necessarily limited to those elements, but may include other elements not expressly listed or elements inherent to such a composition, step, method, article, or apparatus.

[0026] Example 1: Synthesis of 2-benzylamino-2-phenylacetonitrile.

[0027] At room temperature (25°C), 500.0 mg of N-benzylbenzylamine, 0.35 mL of acetone cyanohydrin, and 0.48 mL of 1-butyl-3-methylimidazolium acetate were added to a round-bottom flask equipped with a magnetic stirrer. The reaction time was 20 min. The reaction was monitored by TLC. After the starting material disappeared, the mixture was washed with water, extracted with dichloromethane, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain 555.0 mg of 2-benzylamino-2-phenylacetonitrile, a pale yellow oily liquid with a yield of 97.5%. Figure 1 The image shown is the infrared spectrum of the cyanide product 2-benzylamino-2-phenylacetonitrile synthesized from the raw material N-benzylbenzylamine, with a purity of 99.4%.

[0028] like Figure 2 As shown, the product 2-benzylamino-2-phenylacetonitrile: 1 HNMR(400MHz,Chloroform-d)δ7.66~7.51(m,2H),7.50~7.42(m,4H),7.41(d,J=2.2Hz,1H),7.3 9(d,J=2.1Hz,1H),7.37(s,1H),7.36~7.29(m,1H),4.78(s,1H),4.24~3.87(m,2H),1.86(s,1H).

[0029] Example 2

[0030] The difference between this example and Example 1 is that the ionic liquid used is replaced with 1-ethyl-3-methylimidazolium acetate instead of 1-butyl-3-methylimidazolium acetate. All other steps and parameters are the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 467.9 mg, is a pale yellow oily liquid with a yield of 82.2%.

[0031] Example 3

[0032] The difference between this example and Example 1 is that the ionic liquid used is replaced with 1-butyl-3-methylimidazolium acetate instead of 1-butyl-3-methylimidazolium perchlorate. Other steps and parameters are the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 401.3 mg, is a pale yellow oily liquid with a yield of 70.5%.

[0033] Example 4

[0034] The difference between this example and Example 1 is that the ionic liquid used is replaced with 1-butyl-3-methylimidazolium acetate instead of 1-butyl-3-methylimidazolium bromide. Other steps and parameters are the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 355.2 mg, is a pale yellow oily liquid with a yield of 62.4%.

[0035] Example 5

[0036] The difference between this example and Example 1 is that the amount of ionic liquid used was adjusted from 1-butyl-3-methylimidazolium acetate to 0.24 mL (0.5 equivalents of the substrate N-benzylbenzylamine). Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 285.7 mg, was a pale yellow oily liquid with a yield of 50.2%.

[0037] Example 6

[0038] The difference between this example and Example 1 is that the amount of ionic liquid used was adjusted from 1-butyl-3-methylimidazolium acetate to 0.72 mL (which is 1.5 equivalents of the substrate N-benzylbenzylamine). Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 491.2 mg, was a pale yellow oily liquid with a yield of 86.3%.

[0039] Example 7

[0040] The difference between this example and Example 1 is that the amount of ionic liquid used was adjusted from 1-butyl-3-methylimidazolium acetate to 1.44 mL (equivalent to 2.0 times the substrate N-benzylbenzylamine). Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 446.2 mg, was a pale yellow oily liquid with a yield of 78.4%.

[0041] Example 8

[0042] The difference between this example and Example 1 is that the amount of acetone cyanohydrin used was adjusted to 0.12 mL (0.5 equivalents of the substrate N-benzylbenzylamine). Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 258.4 mg, was a pale yellow oily liquid with a yield of 45.4%.

[0043] Example 9

[0044] The difference between this example and Example 1 is that the amount of acetone cyanohydrin used was adjusted to 0.23 mL (which is 1.0 equivalent of the substrate N-benzylbenzylamine). Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 428.6 mg, was a pale yellow oily liquid with a yield of 75.3%.

[0045] Example 10

[0046] The difference between this example and Example 1 is that the amount of acetone cyanohydrin used was adjusted to 0.46 mL (which is 2.0 equivalents of the substrate N-benzylbenzylamine). Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 494.1 mg, was a pale yellow oily liquid with a yield of 86.8%.

[0047] Example 11

[0048] The difference between this example and Example 1 is that the reaction temperature is 30°C. All other steps and parameters are the same as in Example 1. The obtained product, 2-benzylamino-2-phenylacetonitrile, 445.5 mg, is a pale yellow oily liquid with a yield of 78.3%.

[0049] Example 12

[0050] The difference between this example and Example 1 is that the reaction temperature is 40°C. All other steps and parameters are the same as in Example 1. The obtained product, 2-benzylamino-2-phenylacetonitrile, 399.7 mg, is a pale yellow oily liquid with a yield of 70.2%.

[0051] Example 13

[0052] The difference between this example and Example 1 is that the reaction temperature is 50°C. All other steps and parameters are the same as in Example 1. The resulting product, 2-benzylamino-2-phenylacetonitrile, 339.2 mg, is a pale yellow oily liquid with a yield of 59.6%.

[0053] Example 14: Synthesis of 2-benzylamino-2-tolueneacetonitrile

[0054] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-p-tolylmethylamine, and the amount used was 535.90 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-tolueneacetonitrile, 585.7 mg, was a pale yellow oily liquid with a yield of 96.8% and a purity of 99.5%.

[0055] Product 2-benzylamino-2-tolueneacetonitrile: 1H NMR (300MHz, Chloroform-d) δ7.43~7.39(m,2H),7.39~7.35(m,2H),7.35~7.31(m,2H),7.31~7.25 (m,1H),7.21(s,1H),7.20~7.17(m,1H),4.70(s,1H),4.09~3.87(m,2H),2.35(s,3H),1.26(s,1H).

[0056] Example 15: Synthesis of 2-benzylamino-2-(4-ethylphenyl)acetonitrile

[0057] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-p-ethylphenylmethylamine, and the amount used was 571.65 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-(4-ethylphenyl)acetonitrile, 628.72 mg, was a pale yellow oily liquid with a yield of 98.2% and a purity of 99.1%.

[0058] Product 2-benzylamino-2-(4-ethylphenyl)acetonitrile: 1 H NMR (300MHz, Chloroform-d) δ7.50~7.43(m,3H),7.43~7.39(m,2H),7.39~7.34(m,2H),7.33(q,J=1.9Hz,1H),7.2 8(s,1H),7.24(s,1H),4.74(s,1H),4.14~3.93(m,2H),2.68(q,J=7.6Hz,2H),1.27(d,J=7.6Hz,3H),1.23(s,1H).

[0059] Example 16: Synthesis of 2-benzylamino-2-(4-chlorophenyl)acetonitrile

[0060] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-p-chlorophenylmethylamine, and the amount used was 588.1 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-(4-chlorophenyl)acetonitrile, 625.02 mg, was a pale yellow oily liquid with a yield of 95.1% and a purity of 99.7%.

[0061] Product 2-benzylamino-2-(4-chlorophenyl)acetonitrile: 1H NMR(300MHz,Chloroform-d)δ7.56~7.49(m,2H),7.42(d,J=3.9Hz,2H),7.40(q,J=2.1, 1.5Hz,2H),7.39~7.35(m,2H),7.32(m,1H),4.76(s,1H),4.12~3.92(m,2H),1.9(s,1H).

[0062] Example 17: Synthesis of 2-benzylamino-2-(2-furanyl)acetonitrile

[0063] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-1-(furan-2-yl)methylamine, and the amount used was 474.19 mg. Other steps and parameters were the same as in Example 1. The resulting product was 2-benzylamino-2-(2-furanyl)acetonitrile, 521.63 mg, a brownish-red oily liquid, with a yield of 96.1% and a purity of 99.2%.

[0064] Product 2-benzylamino-2-(2-furanyl)acetonitrile: 1 H NMR(300MHz,Chloroform-d)δ8.22~7.42(m,2H),7.40(s,2H),7.36(d,J=7.4Hz,3 H),7.32(d,J=6.0Hz,1H),4.82(d,J=2.4Hz,1H),4.10~3.92(m,2H),1.62(s,1H).

[0065] Example 18: Synthesis of 2-benzylamino-2-(2-thienyl)acetonitrile

[0066] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-1-(thiophen-2-yl)methylamine, and the amount used was 515.30 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-(2-thiopheno)acetonitrile, 568.70 mg, was a brown oily liquid with a yield of 97.3% and a purity of 99.6%.

[0067] Product 2-benzylamino-2-(2-thienyl)acetonitrile: 1 H NMR(300MHz,Chloroform-d)δ7.46(d,J=1.8Hz,1H),7.42(d,J=5.0Hz,2H),7.38(d,J=5.6Hz,2H) ,7.36(s,2H),7.33~7.29(m,1H),7.17~6.98(m,1H),4.98(s,1H),4.19~3.89(m,2H),1.31(s,1H).

[0068] Example 19: Synthesis of 2-benzylamino-2-(4-fluorophenyl)acetonitrile

[0069] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-p-fluorophenylmethylamine, and the amount used was 545.95 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-(4-fluorophenyl)acetonitrile, 578.21 mg, was a pale yellow oily liquid with a yield of 94.4% and a purity of 99.8%.

[0070] Product 2-benzylamino-2-(4-fluorophenyl)acetonitrile: ¹H NMR (300 MHz, Chloroform-d) δ 7.55 (m, 1H), 7.47–7.40 (m, 2H), 7.38 (d, J = 2.3 Hz, 1H), 7.36 (d, J = 1.7 Hz, 1H), 7.32 (m, 1H), 7.21–7.06 (m, 2H), 4.75 (s, 1H), 4.20–3.89 (m, 2H), 1.28 (s, 1H).

[0071] Example 20: Synthesis of 2-benzylamino-2-(4-isopropylphenyl)acetonitrile

[0072] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-p-isopropylphenylmethylamine, and the amount used was 607.10 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-(4-isopropylphenyl)acetonitrile, 654.46 mg, was a pale yellow oily liquid with a yield of 96.7% and a purity of 99.3%.

[0073] Product 2-benzylamino-2-(4-isopropylphenyl)acetonitrile: 1 HNMR (300MHz, Chloroform-d) δ7.51~7.45(m,2H),7.45~7.41(m,2H),7.41~7.36(m,2H),7.36~7.32(m,1H),7.30(d,J =3.4Hz,1H),7.27(s,1H),4.74(s,1H),4.15~3.94(m,2H),2.96(m,1H),1.33~1.29(m,1H),1.28(s,3H),1.26(s,3H).

[0074] Example 21: Synthesis of 2-benzylamino-2-(3-pyridyl)acetonitrile

[0075] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-1-(3-pyridyl)methylamine, and the amount used was 502.40 mg. Other steps and parameters were the same as in Example 1. The resulting product was 2-benzylamino-2-(3-pyridyl)acetonitrile, 544.16 mg, a brown oily liquid, with a yield of 95.2% and a purity of 99.6%.

[0076] Product 2-benzylamino-2-(3-pyridyl)acetonitrile: 1 H NMR (300MHz, Chloroform-d) δ8.87~8.60(m,2H),7.90(m,1H),7.44~7.39(m,3H),7.39~7.37(m,2H),7.3 6~7.34(m,1H),7.34~7.29(m,1H),4.81(s,1H),4.18~4.05(m,2H),3.98(d,J=13.0Hz,1H),1.27(s,1H).

[0077] Example 22: Synthesis of 2-benzylamino-2-(2-pyridyl)acetonitrile

[0078] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-1-(2-pyridyl)methylamine, and the amount used was 502.40 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-(2-pyridyl)acetonitrile, 551.02 mg, was a brown oily liquid with a yield of 96.4% and a purity of 99.7%.

[0079] Product 2-benzylamino-2-(2-pyridyl)acetonitrile: ¹H NMR (300 MHz, Chloroform-d) δ 8.65 (m, 1H), 7.76 (m, 1H), 7.53–7.46 (m, 1H), 7.47–7.41 (m, 2H), 7.37 (m, 2H), 7.35–7.29 (m, 2H), 4.83 (s, 1H), 4.24–3.96 (m, 2H), 1.38–1.18 (m, 1H).

[0080] Example 23: Synthesis of 2-n-Butylamino-2-tolueneacetonitrile

[0081] The difference between this example and Example 1 is that the substrate was replaced with N-n-butyl-p-toluylmethylamine instead of N-benzylbenzylamine, and the amount used was 448.81 mg. Other steps and parameters were the same as in Example 1. The resulting product was 2-n-butylamino-2-tolueneacetonitrile, 493.66 mg, a brown liquid, with a yield of 95.3% and a purity of 99.5%.

[0082] Product 2-n-Butylamino-2-tolueneacetonitrile: 1 HNMR(300MHz,Chloroform-d)δ7.38(d,J=2.0Hz,2H),7.22~7.15(m,2H),4.72(s ,1H),2.91~2.64(m,2H),2.34(s,3H),1.58~1.18(m,6H),0.91(t,J=7.3Hz,3H).

[0083] Example 24: Synthesis of 2-benzylamino-2-(2-chlorophenyl)acetonitrile

[0084] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-o-chlorophenylmethylamine, and the amount used was 588.1 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-(2-chlorophenyl)acetonitrile, 634.21 mg, was a pale yellow oily liquid with a yield of 96.5% and a purity of 99.3%.

[0085] Product 2-benzylamino-2-(2-chlorophenyl)acetonitrile: ¹H NMR (300 MHz, Chloroform-d) δ 7.70–7.63 (m, 1H), 7.62–7.45 (m, 1H), 7.44 (d, J = 1.8 Hz, 1H), 7.41 (m, 2H), 7.39–7.37 (m, 2H), 7.36–7.29 (m, 2H), 5.07 (s, 1H), 4.22–3.92 (m, 2H), 1.98 (s, 1H).

[0086] Example 25: Synthesis of 2-benzylamino-2-(3-chlorophenyl)acetonitrile

[0087] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-m-chlorophenylmethylamine, and the amount used was 588.1 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-(3-chlorophenyl)acetonitrile, 640.14 mg, was a pale yellow oily liquid with a yield of 97.4% and a purity of 99.4%.

[0088] Product 2-benzylamino-2-(3-chlorophenyl)acetonitrile: 1 HNMR(300MHz,Chloroform-d)δ7.58(m,1H),7.50~7.45(m,1H),7.44(s,1H),7.42(m ,2H),7.38(m,2H),7.37~7.29(m,2H),4.76(s,1H),4.15~3.93(m,2H),1.28(s,1H).

[0089] Example 26: Synthesis of 2-benzylamino-2-(3-cyanophenyl)acetonitrile

[0090] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-benzyl-p-cyanophenylmethylamine, and the amount used was 563.92 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-benzylamino-2-(3-cyanophenyl)acetonitrile, 621.06 mg, was a pale yellow oily liquid with a yield of 98.1% and a purity of 99.8%.

[0091] Product 2-benzylamino-2-(3-cyanophenyl)acetonitrile: ¹H NMR (300 MHz, Chloroform-d) δ 7.73 (s, 4H), 7.41 (m, 2H), 7.39 (d, J = 0.9 Hz, 1H), 7.38–7.35 (m, 1H), 7.35–7.29 (m, 1H), 4.84 (s, 1H), 4.12–3.95 (m, 2H), 1.35–1.18 (m, 1H).

[0092] Example 27: Synthesis of 2-cyclohexylamino-2-tolueneacetonitrile

[0093] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-cyclohexyl-p-toluylmethylamine, and the amount used was 515.49 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-cyclohexylamino-2-tolueneacetonitrile, 558.83 mg, was a pale yellow oily liquid with a yield of 95.6% and a purity of 99.5%.

[0094] Product 2-cyclohexylamino-2-tolueneacetonitrile: 1H NMR (300MHz, Chloroform-d) δ 7.46–7.39 (m, 2H), 7.22 (d, J = 7.9 Hz, 2H), 4.81 (s, 1H), 2.88 (m, 1H), 2.38 (s, 3H), 1.89–1.60 (m, 4H), 1.51–1.15 (m, 6H).

[0095] Example 28: Synthesis of 2-cyclohexylmethylamino-2-tolueneacetonitrile

[0096] The difference between this example and Example 1 is that the substrate was replaced with N-benzylbenzylamine instead of N-cyclohexylmethyl-p-tolylmethylamine, and the amount used was 512.27 mg. Other steps and parameters were the same as in Example 1. The resulting product, 2-cyclohexylmethylamino-2-tolylacetonitrile, 606.81 mg, was a yellow oily liquid with a yield of 97.8% and a purity of 99.7%.

[0097] Product 2-cyclohexylmethylamino-2-tolueneacetonitrile: ¹H NMR (300 MHz, Chloroform-d) δ 7.46–7.40 (m, 2H), 7.22 (d, J = 7.9 Hz, 2H), 4.75 (s, 1H), 2.77–2.54 (m, 2H), 2.39 (s, 3H), 1.85–1.64 (m, 5H), 1.58–1.40 (m, 2H), 1.27–1.18 (m, 2H), 1.07–0.93 (m, 2H).

[0098] Example 29: Synthesis of 2-furanmethylamino-2-tolueneacetonitrile

[0099] The difference between this example and Example 1 is that the substrate was replaced with N-1-(2-furanmethyl)-p-tolylmethylamine, in an amount of 510.09 mg. All other steps and parameters were the same as in Example 1. The resulting product, 2-furanmethylamino-2-tolueneacetonitrile, 570.59 mg, was a yellow oily liquid with a yield of 98.5% and a purity of 99.3%.

[0100] Product 2-furanmethylamino-2-tolueneacetonitrile: 1H NMR (300 MHz, Chloroform-d) δ 7.45–7.39 (m, 3H), 7.21 (s, 2H), 6.33 (m, 2H), 4.74 (s, 1H), 3.97 (d, J = 1.7 Hz, 2H), 2.38 (s, 3H).

[0101] Table 1 Results of the Examples

[0102]

[0103]

[0104] As shown in Examples 1 and 14-29, the method of the present invention starts with readily available imines, uses inexpensive and green acetone cyanohydrin as the cyanide source, and preferably employs 1-butyl-3-methylimidazolium acetate as the ionic liquid. This method rapidly and efficiently achieves the synthesis of imine nucleophilic addition cyanides at room temperature. It exhibits good compatibility with functional groups on aromatic rings and represents a novel, green, and universal synthetic method.

[0105] The above description is merely a preferred embodiment of the present invention. These specific embodiments are different implementations based on the overall concept of the present invention, and the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. An industrial method for preparing α-aminonitrile, characterized in that, The method described: Using imine as a substrate, α-aminonitrile was synthesized by reacting it with acetone cyanohydrin under the action of ionic liquid; The imine is: , , , , , , , , , , , , , , , , ; The synthesized α-aminonitriles include: , , , , , , , , , , , , , , , , ; The ionic liquid is 1-butyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium perchlorate, 1-ethyl-3-methylimidazolium acetate, or 1-butyl-3-methylimidazolium bromide.

2. The method according to claim 1, characterized in that, The amount of acetone cyanohydrin used is 1.0-2.0 times the equivalent of imine, and the amount of ionic liquid used is 0.5-2.0 times the equivalent of imine.

3. The method according to claim 2, characterized in that, The amount of acetone cyanohydrin used is 1.5-2.0 times the equivalent of imine, and the amount of ionic liquid used is 1.0-2.0 times the equivalent of imine.

4. The method according to claim 3, characterized in that, The amount of acetone cyanohydrin used is 1.5 times the equivalent of the ionic liquid.

5. The method according to claim 1, characterized in that, The reaction temperature is 25-50℃.

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